Synthesis of Caerulomycins E and A Analogs for Studying Cytotoxic Activity.

IF 3.4 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-09-22 DOI:10.1002/cmdc.202500594
Pansachon Intamalee, Jesada Maneewong, Natthiya Saehlim, Patamawadee Silalai, Arthit Chairoungdua, Rungnapha Saeeng
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引用次数: 0

Abstract

Caerulomycin A, a marine-derived natural product featuring a bipyridinic core and a substituted oxime functional group, was originally isolated from Streptomyces caeruleus and is known for its antibiotic, antifungal, and cytotoxic properties. In this study, we report the efficient synthesis of caerulomycin A and a series of novel analogs via a five-step synthetic route using readily available reagents. The structural diversification focused on the replacing the methoxy group with various benzyl ether substituents at C-4 and subsequent oxidation and condensation steps at C-6 to generate caerulomycin E and caerulomycin A analogs. These compounds were evaluated for their cytotoxic activity against six human cancer cell lines. Notably, several benzyl ether derivatives exhibited significantly enhanced cytotoxicity compared to the parent compound, with some analogs demonstrating greater potency than the reference drug ellipticine. The structure-activity relationship (SAR) analysis revealed that halogenated substituted benzyl ether groups at C-4 positions played a critical role in modulating cytotoxic activity and selectivity. These findings underscore the potential of synthetic caerulomycin derivatives as promising lead compounds for further development in cancer therapeutics.

绿霉素E和A类似物的合成及其细胞毒活性研究。
Caerulomycin A是一种海洋衍生的天然产物,具有联吡啶核心和取代肟官能团,最初从caeruleus链霉菌中分离出来,具有抗生素、抗真菌和细胞毒性。在这项研究中,我们报道了利用现成的试剂,通过五步合成途径高效地合成了绿霉素A和一系列新的类似物。结构多样化主要集中在C-4上用各种苄基取代甲氧基,随后在C-6上氧化缩合生成卡霉素E和卡霉素A类似物。这些化合物对六种人类癌细胞系的细胞毒活性进行了评价。值得注意的是,与母体化合物相比,一些苯醚衍生物表现出显著增强的细胞毒性,其中一些类似物表现出比参比药物椭圆素更强的效力。构效关系(SAR)分析表明,C-4位置的卤化取代苯醚基团在调节细胞毒性活性和选择性中起关键作用。这些发现强调了合成绿霉素衍生物作为有前途的先导化合物在癌症治疗中进一步发展的潜力。
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来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
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